In vitro sensitivity of Plasmodium falciparum clinical isolates to 4-aminoquinolines in Northeast Nigeria.

Abstract

Background: Widespread dr ug-resistant Plasmodium falciparum strains have challenged the pivotal role played by 4-aminoquinolines, including chloroquine (CQ), which has been delisted for the treatment of malaria in most parts of the world. This study assessed the in vitro sensitivity of P. falciparum clinical isolates (PfCIs) to amodiaquine (AQ) and CQ in Northeast Nigeria.

Materials and methods: PfCIs were collected from subjects with uncomplicated P. falciparum malaria in Azare, Bauchi State and Maiduguri, Borno State following an informed consent. The in vitro sensitivity was assessed by micro-test (MarkIII) method and the IC₅₀ of AQ and CQ was determined using HN-NonLin Version VI.1 software. The reference standard cut-off values for in vitro AQ and CQ resistance of 80 and 160 nmol/l, respectively, were used. Isolates that were inhibited by lower AQ and CQ concentrations were referred to as sensitive.

Results: Valid in vitro assay ^r esults were obtained for 88.9% (80/90) of the PfCIs; Azare had 93.3% (28/30) and Maiduguri had 86.7% (52/60) [χ2 = 0.35; df = 1; p = 0.486]. The geometric mean (GM) IC50 of AQ and CQ were 24.2 nmol/l (95% CI, 10.5 - 49.6 nmol/l) and 39.5 nmol/l (95% CI, 34.5 - 49.6 nmol/l), respectively. The AQ (p = 0.922) and CQ (p = 0.085) GM IC50 were similar between Azare and Maiduguri PfCIs. Only one isolate showed in vitro resistance to AQ giving a sensitivity of 98.8% (79/80) while 17 PfCIs showed in vitro resistance to CQ giving a sensitivity of 78.8% (63/80). The CQ sensitivity was similar between Azare (67.9%; 19/28) and Maiduguri (84.6%; 44/52) PfCIs (χ² = 3.05; df = 1; p = 0.081).

Conclusions: The findings may suggest that the AQ in vitro sensitivity remains high and the isolates in Northeast Nigeria may appear more sensitive to CQ than isolates from other parts. These findings may affect malaria treatment and control policy in Nigeria.